Prescribing patterns of budesonide/formoterol maintenance and reliever therapy in patients with asthma in Sweden
Authors: Christer Janson, Erik Melén, Sofie de Fine Licht, Gunilla Telg, Ekaterina Maslova, Trung N. Tran, Filip Surmont, Fredrik Wiklund, Urban Olsson, Bright I. Nwaru, Magnus Ekström
Journal: Allergy (2023)

Fixed-dose combination of an inhaled corticosteroid (ICS), budesonide (BUD), and a rapid-onset, long-acting β2−agonist (LABA), formoterol (FORM), can be prescribed to patients with mild asthma as an anti-inflammatory reliever and to patients with moderate-to-severe asthma either as maintenance treatment or as maintenance and reliever therapy (MART).1 Although not currently approved for the treatment of patients with mild asthma in Europe, previous studies have demonstrated Symbicort® MART (SMART), a fixed-dose combination of BUD/FORM in a single inhaler, to be more efficacious in reducing the risk of severe exacerbations in moderate-to-severe asthma than conventional maintenance treatments that rely on as-needed short-acting β2-agonist (SABA), with similar improvements in asthma control as comparators.2-4 In addition, results from a recent analysis that quantified the environmental impact of ICS/FORM MART and ICS-based maintenance plus SABA inhalers in the United Kingdom (UK) reported that MART had a lower carbon footprint (dry powder inhaler [DPI]: 7 carbon dioxide equivalent [CO2e] kg/patient/year; pressurised metered-dose inhaler [pMDI]: 116 CO2e kg/patient/year) compared with ICS-based maintenance plus SABA inhalers (DPI: 119 CO2e kg/patient/year; pMDI: 242 CO2e kg/patient/year).5 Real-world data evaluating SMART prescriptions are scarce.6, 7 This population-based study was conducted to gain insight into the prescription patterns of SMART for patients with asthma in Sweden. We aimed to identify physician-indicated SMART as well as other BUD/FORM (Symbicort®) dosing regimens by accessing nationwide data of patients (12–45 years) with asthma and ≥1 BUD/FORM claim(s), that is, prescriptions dispensed from a pharmacy, from Swedish registers during 2006–2015. Claims of SABA and maintenance medications were examined in a 12-month follow-up period. Prescriptions of BUD/FORM generics were not evaluated in this study. For detailed methodology, please see the Supporting Information and Figure S1. Of 52,001 patients evaluated, 4495 (8.6%) were, according to the dosing information, prescribed SMART (intended SMART users); 19,832 (38.1%), adjustable-dose BUD/FORM maintenance; 23,463 (45.1%), fixed-dose BUD/FORM maintenance; 2496 (4.8%), intermittent BUD/FORM; and 1715 (3.3%) received prescriptions with no or unclear dosing information (Table 1). During follow-up, 22.8% of intended SMART users also claimed SABA, which may reflect the patient's psychological dependence on rescue medication, the presence of comorbidities, or poor patient-physician communication.8-10 Alternatively, the coprescription of SABA with SMART may be attributed to pre-exercise use to minimise or prevent symptoms of exercise-induced bronchoconstriction.11 Among patients prescribed adjustable-dose or fixed-dose BUD/FORM maintenance treatment with as-needed SABA, 69.4% did not claim SABA during the 12-month follow-up, suggesting that these patients may have followed the SMART regimen by choice, had well-controlled asthma, or had adapted to their symptoms. Specifically, 69.8%, 67.7%, and 69.0% of patients prescribed adjustable-dose BUD/FORM maintenance, fixed-dose BUD/FORM maintenance, and intermittent BUD/FORM, respectively, did not claim SABA during follow-up (Table 1). This is in contrast with results from the multi-country, cross-sectional SABA use IN Asthma (SABINA) III study, which was conducted in 8351 patients across 24 countries in five continents and where zero SABA prescriptions were reported in only 37.8% of patients.12 Whilst such differences in SABA prescribing practices globally may reflect national health care and medication reimbursement policies and diverse management practices, such disparities may also be due to inherent differences in study design. In this analysis from Sweden, medication use was based on prescriptions dispensed from a pharmacy; in contrast, data from the SABINA III study were based on prescription data only, which may not always reflect prescription collection. In addition, all patients included in this analysis had at least one prescription claim for BUD/FORM, which may have contributed to better-controlled asthma, whereas SABINA III also included patients who were not prescribed maintenance therapy. As such, the high percentage of patients who reported zero SABA prescriptions in this analysis may not be generalisable to other patient populations. This nationwide analysis suggests that the prevalence of SMART prescriptions is low in Sweden, wherein only 8.6% of patients prescribed Symbicort® for asthma had a documented prescription for physician-indicated SMART; however, BUD/FORM without SABA use was more common. Furthermore, possible discrepancies were observed between physician-issued prescriptions and subsequent medication claims by patients. Among intended SMART users, 22.8% claimed SABA inhalers and 36.8% did not claim BUD/FORM inhalers at follow-up, (Table 2). During follow-up, ICS-containing therapy, other than BUD/FORM, was claimed by 64.9% of intended SMART users without SABA claims versus 88.5% of those with SABA claims (Table 2). BUD/FORM was not claimed by 36.8% of intended SMART users without SABA, and ≥4 BUD/FORM inhalers were claimed by only 13.0% of intended SMART users without SABA claims, indicating potential noncompliance with SMART dosing recommendations (Table 2). A similar trend for ≥4 BUD/FORM prescription claims was observed across all other prescription groups. Moreover, in the same groups, the number of BUD/FORM claims was low, suggesting that these patients were likely using BUD/FORM as an anti-inflammatory reliever or had low adherence to the prescribed treatment. Consistent with previous studies from the UK,6, 7 our analysis reported inadequate BUD/FORM prescription claims in the follow-up period. A UK-based study with a 6-month follow-up, which included data from 2484 medication records, reported SMART prescribing to be uncommon among patients (n = 70 [2.8%]).6 Similarly, another UK-based study evaluated the frequency of SMART prescriptions by general practitioners during a 1-year follow-up period and reported infrequent prescription of the SMART dosing regimen in patients (1.2%–1.4%) and an insufficient number of BUD/FORM prescription claims for consistent SMART dosing.7 This same study also reported coprescription of SABA and SMART in more than half of all patients (53%), which is more than twice that reported in our analysis (22.8%). Such differences may be explained by variations in the levels of asthma control reported in the UK and Sweden.13, 14 Nevertheless, the coprescription of SABA with SMART observed in our analysis may reflect a lack of physician awareness and knowledge on the SMART approach for optimising asthma treatment, unclear documentation of dosing instructions, or pre-exercise SABA use.6, 11, 15 Our findings support the need for clear documentation on the appropriate use of inhaled prescription therapies by physicians, adequate physician-patient communication, and education of physicians and patients on guideline-recommended SMART dosing to improve adherence to prescribed treatment regimens and obtain the clinical and environmental benefits of MART therapy. Medical writing and editorial support was provided by Tejaswini Subbannayya, PhD, of Cactus Life Sciences (part of Cactus Communications) in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). This support was fully funded by AstraZeneca. AstraZeneca funded the study; was involved in the study design, protocol development, study conduct, and statistical analysis; and was given the opportunity to review the manuscript before submission. Christer Janson has received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline PLC, Novartis, and Teva outside the submitted work. Erik Melén has received personal fees from AstraZeneca, Chiesi, Novartis, and Sanofi outside the submitted work. Gunilla Telg is a full-time employee of AstraZeneca. Sofie de Fine Licht, Ekaterina Maslova, Trung N. Tran, and Filip Surmont are full-time employees of AstraZeneca and own stock in AstraZeneca. Fredrik Wiklund and Urban Olsson are employees of Statisticon, of which AstraZeneca is a client. Magnus Ekström has received personal fees from AstraZeneca. Bright I. Nwaru has received personal fees from AstraZeneca. Data S1. 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